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Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer (BC). Thus, early detection and accurate diagnosis of this cancer are crucial for improving the survival rate of patients. Specific microRNAs (miRNAs) have been implicated in the occurrence, proliferation, and metastasis of TNBC. Addressing this need, our study developed a biosensor platform for early and accurate TNBC diagnosis by integrating electrochemiluminescence (ECL) technology with a DNA sensing strategy. Specifically, synthesized positively charged carbon dots (CDs) were used to neutralize the electrostatic repulsion between DNA strands and facilitate the assembly of DNA triangular prisms (DNA TP-CDs). Hairpins were then incorporated into the DNA TP-CDs to form the final DNA crown structure. The early TNBC biomarker, microRNA-93–3p (miR-93–3p), allowed for the binding between the DNA Crown and the DNA track on the electrode and initiated the ECL signal. Subsequently, microRNA-210 (miR-210) unlocked the DNA tripedal walker, and its movement on the DNA Crown eventually quenched the ECL signal, enabling accurate TNBC diagnosis and tumor stage assessment. Our proposed biosensor had satisfactory sensing efficiency due to the ordered DNA track and rapid-moving DNA walker. The data revealed a good linear relationship between the ECL signals and the logarithm of miRNA concentrations, with miR-93–3p having a detection limit of 31.04 aM and miR-210 having a detection limit of 7.69 aM. The biosensor also showed satisfactory performance in serum samples and cells. Taken together, this study hopes to provide ideas and applications for clinical diagnosis as well as the personalized treatment of TNBC.

Current diagnostic methods for thyroid diseases, including blood tests, ultrasound, and biopsy, always have difficulty diagnosing thyroiditis accurately, occasionally mistaking it for thyroid cancer. To address this clinical challenge, we developed Ox-PGP1, a novel fluorescent probe realizing rapid, noninvasive, and real-time diagnostic techniques. This is the first imaging tool capable of noninvasively distinguishing between thyroiditis and thyroid cancer. Ox-PGP1 was introduced as a fluorescent probe custom-built for the specific detection and quantification of pyroglutamate aminopeptidase 1 (PGP-1), a known pivotal biomarker of inflammation. Ox-PGP1 overcame the disadvantages of traditional enzyme-responsive fluorescent probes that relied on the intramolecular charge transfer (ICT) mechanism, including the issue of high background fluorescence, while offering exceptional photostability under laser irradiation. The spectral properties of Ox-PGP1 were meticulously optimized to enhance its biocompatibility. Furthermore, the low limit of detection (LOD) of Ox-PGP1 was determined to be 0.09 μg/mL, which demonstrated its remarkable sensitivity and precision. Both cellular and in vivoexperiments validated the capacity of Ox-PGP1 for accurate differentiation between normal, inflammatory, and cancerous thyroid cells. Furthermore, Ox-PGP1 showed the potential to rapidly and sensitively differentiate between autoimmune thyroiditis and anaplastic thyroid carcinoma in a mouse model, achieving results in just 5 min. The successful design and application of Ox-PGP1 represent a substantial advancement in technology over traditional diagnostic approaches, potentially enabling earlier interventions for thyroid diseases.

Breast cancer remains the most frequently diagnosed cancer globally, and the metastasis of this malignancy is the primary cause of mortality in breast cancer patients. Hence, prompt diagnosis and timely detection of metastatic breast cancer are critical for effective therapeutic intervention. Both progression and metastasis of this malignancy are closely associated with aberrant expression of specific microRNAs (miRNAs) and enzymes. To facilitate breast cancer diagnosis and concomitant identification of metastatic breast cancer, we have engineered an innovative electrochemiluminescence (ECL)-based sensing platform integrated with enzyme-free DNA amplification circuits for dual functionality. Specifically, microRNA-21 (miR-21) is employed as a biomarker for breast cancer, and miR-21 induces the quenching of the ECL signal from luminophores via a strategically designed catalytic three-hairpin assembly (CTHA) circuit. Subsequently, miR-105 levels are measured via toehold-mediated strand displacement reactions (TSDR). Here, miR-105 restores the initially quenched ECL signal, enabling the assessment of the metastatic propensity. Our experimental data demonstrate that the devised ECL biosensor offers broad linear detection ranges and low detection limits for both miR-21 and miR-105. Importantly, our novel platform was also successfully validated by using cellular and serum samples. This biosensor not only discriminates breast cancer cell lines MCF-7 and MDA-MB-231 from nonbreast cancer cells like HepG2, TPC-1, and HeLa, but it also distinguishes between malignant MCF-7 and metastatic MDA-MB-231 cells. Consequently, our novel approach holds significant promise for clinical applications and precise cancer screening.

Early detection and effective treatment of thyroid cancer are vital due to the aggressiveness and high mortality rate of the cancer. Nevertheless, the exploration of dipeptidyl peptidase-IV (DPP-IV) as a biomarker for thyroid diseases has not been widely conducted. In this study, we developed a novel non-π-conjugated near-infrared fluorescent probe, MB-DPP4, specifically designed to visualize and detect endogenous DPP-IV. Traditional DPP-IV-specific fluorescent probes rely primarily on the intramolecular charge transfer mechanism. For this reason, these probes are often hampered by high background levels that can inhibit their ability to achieve a fluorescence turn-on effect. MB-DPP4 successfully surmounts several drawbacks of traditional DPP-IV probes, boasting unique features such as exceptional selectivity, ultrahigh sensitivity (0.29 ng/mL), innovative structure, low background, and long-wavelength fluorescence. MB-DPP4 is an “off–on” chemosensor that exhibits strong fluorescence at 715 nm and releases a methylene blue (MB) fluorophore upon interacting with DPP-IV, resulting in a visible color change from colorless to blue. Given these remarkable attributes, MB-DPP4 shows great promise as a versatile tool for advancing research on biological processes and for evaluating the physiological roles of DPP-IV in living systems. Finally, we conducted a comprehensive investigation of DPP-IV expression in human serum, urine, thyroid cells, and mouse thyroid tumor models. Our findings could potentially establish a foundation for the early diagnosis and treatment of thyroid diseases.

Cancer surgery remains a mainstay in clinical treatment. However, the efficacy of subsequent therapies largely depends on the precise evaluation of postoperative prognoses, underscoring the critical need for a comprehensive and accurate assessment of surgical outcomes. Nanoprobes targeting tumors offer a promising solution for visual prognostic assessment. In this study, we developed a “Spindle Monitor” system, designated as APPADs (Au NBPs@PDA-pep-AS1411-Dox), composed of core–shell nanoparticles. The core was made up of gold nanobipyramids (Au NBPs), coated with polydopamine (PDA), and subsequently loaded with peptide chains, AS1411, and doxorubicin (Dox). Upon deployment in the acidic tumor microenvironment (TME), APPADs released substantial amounts of Dox, initiating the apoptotic process. This triggered the activity of caspase-3, which is a crucial executor in the apoptotic pathway. Consequently, DEVD, a specific recognition site for caspase-3, was cleaved, enabling the disconnection of FITC-conjugated peptide chains and the recovery of fluorescence. Through assessing this fluorescence imaging effect, local laser irradiation could be precisely guided to the postoperative site, facilitating a synergistic combination of photothermal therapy and chemotherapy. Specifically, our “Spindle Monitor” APPADs had been validated to achieve accurate fluorescence imaging in vitroand in vivo, which demonstrated its potential value as a versatile tool for evaluating postoperative prognosis in surgical treatments, such as thyroid cancer, and assessing chemotherapy efficacy in difficult cases, like late-stage osteosarcoma. This promising tool lays a good foundation for development in visual prognosis evaluation after tumor surgery.

Fluorescence imaging-guided diagnostics is one of the most promising approaches for facile detection of tumors in situowing to its simple operation and non-invasiveness. As a crucial biomarker for primary ovarian cancers, β-galactosidase (β-gal) has been demonstrated to be the significant molecular target for visualization of ovarian tumors. Herein, a membrane-permeable fluorescent chemosensor (namely, LAN-βgal) was synthesized for β-gal-specific detection using the d-galactose residue as a specific recognition unit and LAN-OH (ΦF= 0.47) as a fluorophore. After β-gal was digested, the fluorescence of the initially quenched LAN-βgal (ΦF< 0.001) was enhanced by up to more than 2000-fold, which exceeded the fluorescence enhancement of other previously reported probes. We also demonstrated that the chemosensor LAN-βgal could visualize endogenous β-gal and distinguish ovarian cancer cells from normal ovarian cells. Further, the chemosensor LAN-βgal was successfully applied to visualize the back tumor-bearing mouse model and peritoneal metastatic ovarian cancer model in vivo. More importantly, through in situspraying, the proposed chemosensor was successfully employed to assist in the surgical resection of ovarian cancer tumors due to its high tumor-to-normal (T/N) tissue fluorescence ratio of 218. To the best of our knowledge, this is the highest T/N tissue fluorescence ratio ever reported. We believe that the LAN-βgal chemosensor can be utilized as a new tool for the clinical diagnosis and treatment of ovarian cancer.

Vanin-1 is a pantetheine hydrolase that plays a key role in inflammatory diseases. Effective tools for noninvasive, real-time monitoring of Vanin-1 are lacking, largely due to background fluorescence interference in existing probes. To address this issue, we developed a dual-modal fluorescent and colorimetric probe, MB-Van1, to detect Vanin-1 with high sensitivity and selectivity. MB-Van1 has a structure optimized to exhibit nearly zero background fluorescence, resulting in a high signal-to-noise ratio that enables the accurate detection of Vanin-1 activity in various biological tissues. In vitroexperiments demonstrated that MB-Van1 had a detection limit as low as 0.031 ng/mL in the fluorescence mode. We successfully employ MB-Van1 to observe elevated Vanin-1 levels in inflammatory tissues of various mouse models of rheumatoid arthritis (RA), drug-induced liver injury (DILI), and nonsteroidal anti-inflammatory drug (NSAID) enteropathy models, within only 5 min. This advancement provides a novel approach for monitoring the dynamic changes of Vanin-1 during inflammation, offering new strategies for the early diagnosis and therapeutic assessment of other related diseases.

A kind of novel environmental-friendly composite absorbent material was designed and prepared in this paper. Nanoscale metal-organic frameworks(MOFs) were embedded in the skeleton of cotton micro fibrillated cellulose. By scanning electron microscope(SEM), we observed that a large number of MOFs were attached to the cellulose skeleton. In addition, under the condition of 1800 r/min vortex, the structure of the composite material was stable and was not easily damaged by external forces. The water contact angle test showed that the composite material had excellent hydrophilicity and could be used for the adsorption of pollutants. Then, the material was characterized by energy dispersive X-ray spectroscopy(EDX), X-ray diffraction(XRD), Fourier transform infrared spectroscopy(FTIR) and BET adsorption. Through verification, the material had very stable reusability(n=10). The composite material was applied to the solid phase extraction of water samples, such as rain water, toning water and fruit juice, and was quantitatively analyzed by high performance liquid chromatography(HPLC)-UV. This method was then applied to the extraction of four parabens(methyl-, ethyl-, propyl-, and butylparaben) from real samples, yielding limits of detection(LODs) of 0.29–0.58 ng/mL. The linear range was 2–500 ng/mL. The inter-day and intra-day recoveries were 90.7%–106.0% and 87.1%–109.3%, respectively(relative standard deviation<10.8%).

Although high-performance donor–acceptor (D–A)-type polymers have received much attention as an important class of electrochromic (EC) materials, the related studies have mostly focused on the influence of D and A units on the band gap, onset potential, and switching time, leaving the effect of D–A structures on cycling lifetime underexplored. Herein, we design and synthesize a series of poly(aryl amino sulfone)s (PAASs) as D–A polymers with triphenylamine-based donor units and the sulfone moiety as the acceptor unit. As a result, we present new rules to design and develop D–A structure polymers with high EC cycling stability: (1) the electron-donating and -withdrawing abilities of the donor and acceptor should be balanced during the electrochemical cycle process, and this balance can be measured by the ratio of Jred/Jox; (2) the D–A structure should benefit to generate lower Eonset. By these design rules, the best-performing polymer PAAS-TPPA-OMe exhibits an excellent long-term cycling stability (over 3,900 cycles), low onset potential (0.26 V), fast switching time (6.0/4.3 s for the EC process), high contrast (87% at 688 nm and 94% at 928 nm), and high coloration efficiency (500 cm2C–1at 688 nm and 1131 cm2C–1at 928 nm).

Inflammation can affect the progression of cancer at tumor sites, such as in osteosarcoma, by intensifying metastasis and complicating outcomes. The current diagnostic methods lack the specificity and sensitivity required for early and accurate detection, particularly in differentiating between inflammation-induced changes and tumor activities. To address this, a novel “hedgehog ball”-shaped nanoprobe, Fe3O4@Au-pep-CQDs, was developed and designed to enhance the detection of caspase-1, a key marker of inflammation. This magnetic nanoprobe facilitates simultaneous fluorescence (FL) and electrochemiluminescence (ECL) detection. Magnetic separation minimizes the quenching of nanoparticles in solution and eliminates the need for frequent electrode replacement in ECL tests, thereby simplifying diagnostic procedures. The experimental results showed that in the detection of caspase-1, the nanoprobe had a detection limit of 0.029 U/mL (FL) and 0.033 U/mL (ECL) and had a dynamic range of 0.05 to 1.0 U/mL. Additionally, the nanoprobe achieved high recovery rates of 94.36 to 102.44% (FL) and 94.36–100.12% (ECL) in spiked biological samples. Furthermore, the nanoprobe’s capabilities were extended to in vivo bioimaging to provide direct, intuitive visualization of biological processes. These novel nanoprobes were able to significantly enhance the accurate detection of inflammation at tumor sites, thereby optimizing both diagnostic and therapeutic strategies.

The aggressive nature and high mortality rate of lung cancer underscore the imperative need for early diagnosis of the disease. Thus, aminopeptidase N (APN), a potential biomarker for lung cancer, should be thoroughly investigated in this context. This report describes the development of HA-apn, a novel near-infrared fluorescent probe, specifically engineered for the sensitive detection of endogenous APN. Characterized by its high selectivity, straightforward molecular architecture, and suitable optical properties, including a long-wavelength emission at 835 nm and a large Stokes shift of 285 nm, HA-apnhad high efficacy in identifying overexpressed APN in tumor cells, which shows its potential in pinpointing malignancies. To further validate its applicability and effectiveness in facilitating the direct and enhanced visualization of pulmonary alterations, an in situlung cancer mouse model was employed. Notably, HA-apnwas applied for in vivoimaging of APN activity in the lung cancer mouse model receiving the probe through aerosol inhalation, and rapid and precise diagnostic results were achieved within 30 min post-administration. Overall, HA-apncan be applied as an effective, non-intrusive tool for the rapid and accurate detection of pulmonary conditions.

Bacterial vegetative cells turn into metabolically dormant spores in certain environmental situations. Once suitable conditions trigger the germination of spores belonging to the pathogenic bacterial category, public safety and environmental hygiene will be threatened, and lives will even be endangered when encountering fatal ones. Instant identification of pathogenic bacterial spores remains a challenging task, since most current approaches belonging to complicated biological methods unsuitable for onsite sensing or emerging alternative chemical techniques are still inseparable from professional instruments. Here we developed a polychromatic fluorescent nanoprobe for ratiometric detection and visual inspection of the pathogenic bacterial spore biomarker, dipicolinic acid (DPA), realizing rapidly accurate screening of pathogenic bacterial spores such as Bacillus anthracisspores. The nanoprobe is made of aminoclay-coated silicon nanoparticles and functionalized with europium ions, exhibiting selective and sensitive response toward DPA and Bacillus subtilisspores (simulants for Bacillus anthracisspores) with excellent linearity. The proposed sensing strategy allowing spore determination of as few as 0.3 × 105CFU/mL within 10 s was further applied to real environmental sample detection with good accuracy and reliability. Visual quantitative determination can be achieved by analyzing the RGB values of the corresponding test solution color via a color recognition APP on a smartphone. Different test samples can be photographed at the same time, hence the efficient accomplishment of examining bulk samples within minutes. Potentially employed in various on-site sensing occasions, this strategy may develop into a powerful means for distinguishing hazardous pathogens to facilitate timely and proper actions of dealing with multifarious security issues.

Traditional molecular imaging tools used for detecting liver diseases own several drawbacks, such as poor optical performance and limited applicability. Monitoring the concentration of leucine aminopeptidase (LAP), which is closely related to liver diseases such as liver cancer and liver injury, and analyzing it in diagnosis, drug evaluation, and surgical treatment is still a challenging task. Herein, we construct an intramolecular charge-transfer mechanism-based, ultrasensitive, near-infrared fluorescent probe (LAN-lap) for dynamic monitoring of LAP fluctuations in living systems. LAN-lap, with high specificity, stability, sensitivity, and water solubility, can achieve in vitro monitoring of LAP through both fluorescence and colorimetric methods. Moreover, LAN-lap can successfully be used for the localization imaging of endogenous LAP, confirming the upregulation of LAP expression in liver cancer and liver injury cells. In addition, LAN-lap can realize the imaging of liver tumors in living organisms. Meanwhile, it can intuitively present the degree of drug-induced liver injury, achieving semi-quantitative imaging evaluation of the hepatotoxicity of two drugs. Furthermore, LAN-lap can track liver cancer tumors in mice with peritoneal metastasis and can assist in fluorescence-guided surgical resection of liver cancer tumors. This multifunctional LAN-lap probe could play an important role in facilitating simultaneous diagnoses, imaging, and synergistic surgical navigation to achieve better point-of-care therapeutic efficacy.

As known biomarkers of kidney diseases, N-acetyl-β-d-glucosaminidase (NAG) and β-galactosidase (β-GAL) are of great importance for the diagnosis and treatment of diseases. The feasibility of using multiplex sensing methods to simultaneously report the outcome of the two enzymes in the same sample is even more alluring. Herein, we establish a simple sensing platform for the concurrent detection of NAG and β-GAL using silicon nanoparticles (SiNPs) as a fluorescent indicator synthesized by a one-pot hydrothermal route. p-Nitrophenol (PNP), as a common enzymatic hydrolysis product of the two enzymes, led to the attenuation of fluorometric signal caused by the inner filter effect on SiNPs, the enhancement of colorimetric signal due to the increase of intensity of the characteristic absorption peak at around 400 nm with increasing reaction time, and the changes of RGB values of images obtained through a color recognition application on a smartphone. The fluorometric/colorimetric approach combined with the smartphone-assisted RGB mode was able to detect NAG and β-GAL with good linear response. Applying this optical sensing platform to clinical urine samples, we found that the two indicators in healthy individuals and patients (glomerulonephritis) with kidney diseases were significantly different. By expanding to other renal lesion-related specimens, this tool may show great potentials in clinical diagnosis and visual inspection.

Alkaline phosphatase (ALP) is widely present in the human body and is an important biomarker. Numerous ALP detection studies have been carried out, and ascorbic acid (AA) is often used as the reducing component in the sensors to monitor ALP levels since it can be produced from ascorbic acid 2-phosphate (AA2P) hydrolysis in the presence of ALP. However, it is well-known that AA is a strong reducing agent and can be easily oxidized. The disproportion between oxidized AA and reduced AA reactions results in the generation of AA free radicals with single electrons that may lead to inaccurate results in assays. To solve this problem, we synthesized a core–shell metal–organic framework sensor (PATP-Au@ZIF-8 NP) and used it as a sensitive and accurate ALP detection sensor with self-triggered control of phosphate ions (Pi) to avoid the potential inaccuracy of the method that uses AA as the reducing component. By establishing a physical shell on the surface of the gold nanoparticles (Au NPs), the sensor not only can eliminate the random assembly of metal nanoparticles caused by plasma exposure but also can generate self-triggering of Pi caused by ALP. Pi can decompose ZIF-8 through coordination with Zn2+and thus can destroy the ZIF-8 shell structure of the prepared PAZ NPs. Au NPs are released and then become aggregated, in turn causing the SERS “hot spot” area to increase. The enhancement of the SERS signals was found to be directly associated with the level of Pi released from ALP-triggered hydrolysis. The response of the strategy was linear at ALP concentrations ranging from 0.1 to 150 mU/mL (r= 0.996) with a detection limit of 0.03 mU/mL. Lastly, the developed strategy was employed in the evaluation of ALP inhibitors, and the possibility to implement the developed SERS strategy for rapid and selective analysis of ALP in human serum was demonstrated.

Fluorescein-rhodamine 6G(Flu-Rh) was synthesized and used as the fluorescence probe for pH measurement based on fluorescence resonance energy transfer(FRET). In the probe, fluorescein fluorophore and pH-sensitive rhodamine 6G hydrazide were used as FRET donor and acceptor, respectively. The values of acidity constant(pKa) and fluorescence quantum yield(Φ) of Flu-Rh were 3.71 and 0.72, respectively. The fluorescence efficiency of Flu-Rh remains almost constant when the pH value of the sample solution changed 10 times in a range of 4.78–7.03 continuously. The present probe is simple and easy-to-use for the pH measurement in acidic media.

Silver nanoparticles (AgNPs) were synthesized by a classic method. The surface-enhanced Raman scattering (SERS) activity of the as-synthesized substrates was evaluated by measuring the SERS signals of several different target analytes. The influence of starch concentration on AgNPs was studied and 1.00% (w/v) of starch was selected. The starch-coated AgNPs displayed a higher stability than the classic AgNPs. The practical application of the starch-coated SERS substrate was evaluated by determination of melamine and malachite green. Under the optimal conditions, melamine and malachite green were determined in the ranges of 2.00–50.0 μg L−1and 0.500–35.0 μg L−1with correlation coefficients of 0.9992 and 0.9979, and the detection limits were 0.600 μg L−1and 0.080 μg L−1, respectively. The recoveries of melamine in spiked milk samples and malachite green in water samples were 94–104% and 96–107%, respectively. These results foresee promising application of starch-coated AgNPs as sensitive SERS substrates in both food and environmental water.

In this study, a simple and efficient method based on surface-enhanced Raman spectroscopy (SERS) was developed to detect thiocyanate ion (SCN−) and melamine in milk and milk powder. Silver nanoparticles (AgNPs), sodium chloride (NaCl) and sodium hydroxide (NaOH) were used as the substrate, the aggregating agent and the alkaline adjusting agent for the SERS process, respectively. The SERS peak intensity at 445 cm−1was measured under low NaCl concentration for determining SCN−, followed by the measurement of the SERS peak intensity at 704 cm−1under high NaCl concentration for determining melamine. The determination conditions for SERS, including the amount of AgNPs, NaCl and NaOH, and the mixing time before measurement, were optimized. By the present method, good linear responses were obtained for SCN−and melamine in the concentration ranges of 2.00–191.00 mg L−1and 0.01–4.80 mg L−1respectively, with correlation coefficients higher than 0.998. The present method was successfully applied to the simultaneous determination of SCN−and melamine in four spiked milk samples and three certified milk powder samples. The recoveries of SCN−and melamine in spiked milk samples were 95.15–100.47% and 94.43–102.84%, respectively. The relative standard deviations (RSDs) for determining melamine in certified milk powder samples were lower than 1.6%.

A novel, simple and ultra-sensitive method, for rapid detection of trace malachite green (MG) in environmental water using cloud point extraction (CPE) coupled with surface-enhanced Raman scattering (SERS) is described. The colloidal gold nanoparticles (AuNPs) were synthesized by reduction of chloroauric acid (HAuCl4) with trisodium citrate and were used as SERS substrates. The SERS substrates were found to produce enhancement factors of 1.52 × 106for MG by employing the SERS peak at 1175 cm−1. After the optimization of SERS conditions including the volumes of ethanol, colloidal AuNPs and HCl, the present method was linear for MG at 1175 cm−1and 1618 cm−1over the concentration range of 0.5–35.0 μg L−1and 2.5–40.0 μg L−1, with the correlation coefficients (r) of 0.9971 and 0.9960. The limits of detection (LODs) were 0.10 μg L−1and 0.70 μg L−1, and the intra- and inter-day relative standard deviations (RSDs) of detection were in the range of 2.0–2.5% and 1.9–3.2% at 1175 cm−1and 1618 cm−1, respectively. Recoveries obtained by analyzing 4 spiked environmental water samples at 2 levels were between 93.1 and 106.0%.